Biju,M P; Paulose,C S(Department of Biotechnology, September 27, 1997)
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Abstract:
Kinetic parameters of brain glutamate dehydrogenase (GDH) were compared in the brain
stem, cerebellum and cerebral cortex of three weeks and one year old streptozotocin (STZ)
induced four day diabetic rats with respective controls. A single intrafemoral dose of STZ
(60mg/Kg body weight) was administered to induce diabetes in both age groups. After four days
the blood glucose levels showed a significant increase in the diabetic animals of both age groups
compared with the respective controls. The increase in blood glucose was significant in one year
old compared to the three weeks old diabetic rats. The Vmm of the enzyme was decreased in all
the brain regions studied, of the three weeks old diabetic rats without any significant change in
the Km. In the adult the Vmax of GDH was increased in cerebellum and brain stem but was
unchanged in the cerebral cortex. The K. was unchanged in cerebellum and cerebral cortex but
was increased in the brain stem. These results suggest there may be an important regulatory role
of the glutamate pathway in brain neural network disturbances and neuronal degeneration in
diabetes as a function of age.
Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous
seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated
with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory
action on cerebellar function through 5HT2C receptors. 5-HT2C receptors are novel targets for developing anticonvulsant
drugs. In the present study, we investigated the changes in the 5-HT2C receptors binding and gene
expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a
significant down regulation of the 5-HT content (pb0.001), 5-HT2C gene expression (pb0.001) and 5-HT2C
receptor binding (pb0.001) with an increased affinity (pb0.001). Carbamazepine and B. monnieri treatments
to epileptic rats reversed the down regulated 5-HT content (pb0.01), 5-HT2C receptor binding (pb0.001) and
gene expression (pb0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and
recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the
upregulation of 5-HT2C receptor in epileptic rats. This has clinical significance in the management of epilepsy